Formation of the nephric duct

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R-HSA-9830364
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Pathway
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Homo sapiens
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3/5
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Formation of the nephric duct
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The nephric duct originates from nephrogenic cords of intermediate mesoderm by a transition of the cells to epithelium in response to signals from somites and overlying ectoderm (reviewed in Reidy and Rosenblum 2009, Little and McMahon 2012, Khoshdel Rad et al. 2020). Initially, the nephric duct forms within in the pronephros, the first kidney structure, which comprises the nephric duct (the pronephric duct at this time) and connected tubules that empty into it. The second kidney structure, the mesonephros, then forms at the caudal end of the pronephros and contains a segment of the nephric duct, the mesonephric duct (also called the Wolffian duct), with connected proximal and distal tubules attached to nephrons and vascular glomeruli. The mesonephros fuses with the cloaca and contributes to the urinary bladder.
The metanephros then forms and persists as the functional adult kidney. The metanephros originates by the initiation of the ureteric bud from of the caudal end of the mesonephric duct, a process that is driven by molecular interactions between the nephric duct and the adjacent metanephric mesenchyme. The ureteric bud then branches and about a million nephrons, the functional filtration units of the kidney, are formed at the ureteric bud tips by an interaction between the ureteric bud and the metanephric mesenchyme.
The position of kidney formation is determined by the retinoic acid gradient acting through the HOXB4 homeobox transcription factor (inferred from mouse embryos in Preger-Ben Noon et al.2009, reviewed in Marcotte et al. 2014). PAX2, PAX8, and LHX1 are expressed early during the formation of the intermediate mesoderm. Subsequently, expression of LHX1 becomes restricted to the developing renal progenitors and is maintained by PAX2 and PAX8 (inferred from mouse homologs in Boualia et al. 2013). In the developing nephric duct, LHX1 acts with PAX2 and GATA3 to form a self-reinforcing regulatory module based on the mutual activation of LHX1 and GATA3 that drives formation of the nephric duct of the pronephros and mesonephros (inferred from mouse homologs in Boualia et al. 2013, reviewed in Marcotte et al. 2014). LHX1, GATA3, PAX2, and PAX8 then activate several genes involved in differentiation of the nephric duct including EMX2, EVI1, ID4, PLAC8, WFDC2, PCDH19, Nephronectin (NPNT), and the receptor tyrosine kinase RET (reviewed in Marcotte et al. 2014). Subsequent formation of the ureteric bud is regulated by the interaction between GDNF from the metanephric mesenchyme and RET (inferred from mouse homologs in Majumdar et al. 2003) and the interaction between integrin alpha8/beta1 (ITGA8) from the metanephric mesenchyme and NPNT (inferred from mouse homologs in Brandenberger et al. 2001).
Literature References
PubMed ID Title Journal Year
22550230 Mammalian kidney development: principles, progress, and projections

Little, MH, McMahon, AP

Cold Spring Harb Perspect Biol 2012
24104595 Gene regulatory network of renal primordium development

Marcotte, M, Sharma, R, Bouchard, M

Pediatr Nephrol 2014
19439491 Interplay between activin and Hox genes determines the formation of the kidney morphogenetic field

Preger-Ben Noon, E, Barak, H, Guttmann-Raviv, N, Reshef, R

Development 2009
11470831 Identification and characterization of a novel extracellular matrix protein nephronectin that is associated with integrin alpha8beta1 in the embryonic kidney

Brandenberger, R, Schmidt, A, Linton, J, Wang, D, Backus, C, Denda, S, Müller, U, Reichardt, LF

J Cell Biol 2001
19615554 Cell and molecular biology of kidney development

Reidy, KJ, Rosenblum, ND

Semin Nephrol 2009
12783789 Wnt11 and Ret/Gdnf pathways cooperate in regulating ureteric branching during metanephric kidney development

Majumdar, A, Vainio, S, Kispert, A, McMahon, J, McMahon, AP

Development 2003
22942910 Genetic controls and cellular behaviors in branching morphogenesis of the renal collecting system

Costantini, F

Wiley Interdiscip Rev Dev Biol 2012
32266264 Cellular and Molecular Mechanisms of Kidney Development: From the Embryo to the Kidney Organoid

Khoshdel Rad, N, Aghdami, N, Moghadasali, R

Front Cell Dev Biol 2020
23920117 A core transcriptional network composed of Pax2/8, Gata3 and Lim1 regulates key players of pro/mesonephros morphogenesis

Boualia, SK, Gaitan, Y, Tremblay, M, Sharma, R, Cardin, J, Kania, A, Bouchard, M

Dev Biol 2013
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nephric duct formation (0072179)
Authored
May, B  (2023-03-08)
Created
May, B  (2023-03-09)
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